Glucose Counterregulation

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Numerous studies have found that elderly patients with diabetes, when compared with younger patients, have an increased frequency of severe or fatal hypoglycemia (Stepka, Rogala and Czyzyk 1993). A number of studies have evaluated glucose counter-regulation in elderly subjects to try to determine the cause of the increased frequency of hypoglycemia, and some important observations have emerged. Many elderly patients with diabetes have not been educated about the warning symptoms of hypoglycemia and as a consequence do not know how to interpret the symptoms when they occur (Thomson et al 1991). The most important hormone in the defence against hypoglycemia in normal subjects is glucagon. If glucagon responses are deficient, epinephrine becomes important, and growth hormone and cortisol come into pay if hypoglycemia is prolonged for several hours. Gluca-gon and growth hormone responses to hypoglycemia are impaired in healthy elderly subjects and to an even greater extent in older patients with diabetes (Figure 2.7) (Meneilly et al 1994). Even when they are educated about the symptoms of hypoglycemia, the elderly

Figure 2.7 Glucagon and growth hormone (GH) responses to hypoglycemia in healthy young, healthy old and elderly patients with diabetes. Controlled hypoglycemia was induced using the glucose clamp technique. Glucose values at which hormone levels were measured are shown on the top horizontal axis

have reduced awareness of the autonomic warning symptoms (sweating, palpitations, etc.) at glucose levels that would elicit a marked response in younger subjects. Finally, elderly patients have impaired psy-chomotor performance during hypoglycemia, which would prevent them from taking steps to return the blood glucose value to normal even if they were aware that it was low. Thus the increased frequency of hypo-glycemia in the elderly is due to a constellation of abnormalities, including reduced knowledge and awareness of warning symptoms, decreased counter-regulatory hormone secretion and altered psychomotor performance.

The levels of pancreatic polypeptide (PP) is elevated during hypoglycemia, and this response is mediated by the vagus nerve. The role of PP in normal glucose counter-regulation is uncertain, but in younger patients with diabetes reduced PP responses to hypoglycemia are an early marker of autonomic insufficiency. Although elderly patients with diabetes often have evidence of autonomic dysfunction, their PP responses to hypoglycemia are normal (Meneilly 1996). Thus PP responses to hypoglycemia cannot be used to predict autonomic function in elderly patients.

It has been suggested that some younger patients with diabetes, when switched to human from animal insulins, develop hypoglycemic unawareness and an increased frequency of hypoglycemic events. It has been demonstrated that animal insulin results in a greater awareness of the warning symptoms of hypo-glycemia than human insulin in elderly patients with diabetes, although a small clinical trial found no difference in the frequency of hypoglycemic events in elderly patients treated with animal or human insulin (Meneilly, Milberg and Tuokko 1995; Berger 1987). It has been the author's clinical experience that elderly patients treated with human insulin who develop hypoglycemic unawareness and frequent hypoglycemic events on human insulin do better with beef-pork insulin. Pending the results of further studies, animal insulins should continue to be made available for use in the elderly.

Based on the above information, there are a number of interventions that can be proposed to prevent hy-poglycemic events in the elderly. First, it would seem prudent to educate elderly patients about the warning symptoms of hypoglycemia so that they can appreciate them when they occur. Second, consideration should be given to the use of oral agents or insulin preparations that are associated with a lower frequency of hypoglycemic events in the elderly.

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